The present invention relates to a syringe assembly for the quantitative dilution measurement of radioactive injectate and a kit having the same, and more particularly to such an assembly which delivers the injectate with a high precision.
The kit of the present invention facilitates the performance of quantitative radioactivity dilution measurements, such as that performed by the Automated Multi-Point Blood Volume Analyzer described in U.S. Pat. No. 5.02444,231. In such measurements, a precise amount of radioactive tracer is administered to the subject. After dilution of the tracer has occurred, the radioactivity of a sample or samples from the subject is compared to that of a standard prepared from the original injectate. This standard is prepared by diluting an equivalent dose of radiation into a known volume. In the prior art, a technician would prepare the standards manually at the time of the procedure. This has several disadvantages compared with the use of the kit described herein. It is time consuming, subject to technician error, and requires access to a lab with appropriate glassware. It requires handling of a supply of radioactive tracer; and such a supply is likely to have a level of activity many times higher than that contained in a single-use kit, as it is not commercially practical to order radioisotopes in very small amounts.
Various U.S. patents have been issued for kits involving radioactivity, but they all have in common that they are designed to facilitate qualitative studies. For the purposes of the present invention, a qualitative injection is one where a precision of 97% or 98% is sufficient, as is generally the case with a therapeutic injection, or one where a tracer compound is used for imaging purposes. By contrast, a quantitative injection is one where the injectate must be delivered with high precision, at least 99.9% of an expected dose, typically because the subsequent dilution or uptake of the injectate by the subject is used to precisely calculate some numerical value, such as the volume of blood in the subject into which the injectate is diluted (i.e., injected).
U.S. Pat. No. 4,364,376 describes a device for injecting a radioactive bolus into a body. The prior art for a quantitative dilution measurement (the object of the present invention) is similar to the prior art as described therein, with a few changes which reflect the need for a higher degree of precision. Thus, the standard 1 cc syringe would be replaced by a calibrated syringe capable of delivering a precise amount of fluid, and this same calibrated syringe would be used to prepare a plurality of standards by diluting an equivalent injectate into a known volume. By comparing the level of tracer in the standards with the level of tracer in samples taken from the subject, the unknown volume of the subject can be determined. The patented device is an improvement on the prior art qualitative applications for which it was designed, such as imaging, these applications typically using relatively high doses of radiation, and hence justifying the emphasis on improved shielding. Despite its suggestion of a "flow-through" feature, the patented device is inadequate, however, to the task of quantitative dilution measurement because the process of filling the syringe with the injectate through the needle (see FIGS. 3 and 4) is subject to an inherent mechanical variability on the order of 2% or 3%, as well as to technician error.
Each of U.S. Pat. No. 2,671,450, U.S. Pat. No. 4,735,311 and U.S. Pat. No. 2,831,483 discloses an air-lock design. The use of an air-lock mechanism allows the syringe to be pre-filled from the back, thereby avoiding the problem of leakage from the needle. The possibility for technician error is also decreased, as the technician needs only to perform the injection step.
Other patents which deal with radioactivity are only tangentially relevant. U.S. Pat. No. 4,300,569 describes a procedure for radiolabelling red blood cells, as do U.S. Pat. No. 4,471,765 and U.S. Pat. No. 4,372,294. However, the devices disclosed therein are not concerned with delivering a calibrated dosage of an already-labelled blood component (e.g., albumin I-131) in a quantitative study. Thus the disclosed devices lack a "flow-through" design. Even if the apparatus is flushed with a sterile saline solution, there will still inevitably be incomplete delivery of the radioisotope due to the use of the mixing syringes. U.S. Pat. No. 4,874,601 and U.S. Pat. No. 5,021,220 describe kits for producing radiolabelled organic compounds of pharmaceutical purity (such as albumin I-131), but they do not disclose devices for delivering the same quantitatively. U.S. Pat. No. 4,954,239 describes a disposable kit for irrigating an IV line, but not for the quantitative delivery of a calibrated dosage of radioactive tracer. As the syringes described above cannot be washed or "flushed" out, some of the injectate will remain in the volume of the needle and in the syringe. This is adequate for the therapeutic or qualitative diagnostic purposes for which they were designed, but not for the quantitative purpose for which the present kit is designed. Other designs for disposable syringes, such as those disclosed in U.S. Pat. No. 1,589,882, U.S. Pat. No. 2,642,868 and U.S. Pat. No. 3,089,491, share this limitation.
The prior art for syringe design is quite extensive, but nowhere is the combination of the needle air-lock feature and the flow-through mechanism feature found in the context of a quantitative dilution measurement of radioactivity, the combination of these two features in a single syringe design enabling a new function for a disposable syringe--namely, that of quantitative analysis.
Accordingly, an object of the present invention is to provide a syringe assembly combining an air-lock feature and a flow-through mechanism feature.
Another object is to provide such an assembly which enables the syringe assembly to be used for quantitative analysis in the context of a quantitative dilution measurement of radioactivity.
A further object is to provide in one embodiment a disposable kit for delivery of a precise dose of radioactive tracer to a subject with an accuracy of at least 99.9% by weight.